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Quantitative proteomics of bronchoalveolar lavage fluid in idiopathic pulmonary fibrosis.

Publication ,  Journal Article
Foster, MW; Morrison, LD; Todd, JL; Snyder, LD; Thompson, JW; Soderblom, EJ; Plonk, K; Weinhold, KJ; Townsend, R; Minnich, A; Moseley, MA
Published in: J Proteome Res
February 6, 2015

The proteomic analysis of bronchoalveolar lavage fluid (BALF) can give insight into pulmonary disease pathology and response to therapy. Here, we describe the first gel-free quantitative analysis of BALF in idiopathic pulmonary fibrosis (IPF), a chronic and fatal scarring lung disease. We utilized two-dimensional reversed-phase liquid chromatography and ion-mobility-assisted data-independent acquisition (HDMSE) for quantitation of >1000 proteins in immunodepleted BALF from the right middle and lower lobes of normal controls and patients with IPF. Among the analytes that were increased in IPF were well-described mediators of pulmonary fibrosis (osteopontin, MMP7, CXCL7, CCL18), eosinophil- and neutrophil-derived proteins, and proteins associated with fibroblast foci. For additional discovery and targeted validation, BALF was also screened by multiple reaction monitoring (MRM), using the JPT Cytokine SpikeMix library of >400 stable isotope-labeled peptides. A refined MRM assay confirmed the robust expression of osteopontin, and demonstrated, for the first time, upregulation of the pro-fibrotic cytokine, CCL24, in BALF in IPF. These results show the utility of BALF proteomics for the molecular profiling of fibrotic lung diseases and the targeted quantitation of soluble markers of IPF. More generally, this study addresses critical quality control measures that should be widely applicable to BALF profiling in pulmonary disease.

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Published In

J Proteome Res

DOI

EISSN

1535-3907

Publication Date

February 6, 2015

Volume

14

Issue

2

Start / End Page

1238 / 1249

Location

United States

Related Subject Headings

  • Tandem Mass Spectrometry
  • Reproducibility of Results
  • Proteomics
  • Idiopathic Pulmonary Fibrosis
  • Humans
  • Electrophoresis, Polyacrylamide Gel
  • Bronchoalveolar Lavage Fluid
  • Biochemistry & Molecular Biology
  • 34 Chemical sciences
  • 31 Biological sciences
 

Citation

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Foster, M. W., Morrison, L. D., Todd, J. L., Snyder, L. D., Thompson, J. W., Soderblom, E. J., … Moseley, M. A. (2015). Quantitative proteomics of bronchoalveolar lavage fluid in idiopathic pulmonary fibrosis. J Proteome Res, 14(2), 1238–1249. https://doi.org/10.1021/pr501149m
Foster, Matthew W., Lake D. Morrison, Jamie L. Todd, Laurie D. Snyder, J Will Thompson, Erik J. Soderblom, Kelly Plonk, et al. “Quantitative proteomics of bronchoalveolar lavage fluid in idiopathic pulmonary fibrosis.J Proteome Res 14, no. 2 (February 6, 2015): 1238–49. https://doi.org/10.1021/pr501149m.
Foster MW, Morrison LD, Todd JL, Snyder LD, Thompson JW, Soderblom EJ, et al. Quantitative proteomics of bronchoalveolar lavage fluid in idiopathic pulmonary fibrosis. J Proteome Res. 2015 Feb 6;14(2):1238–49.
Foster, Matthew W., et al. “Quantitative proteomics of bronchoalveolar lavage fluid in idiopathic pulmonary fibrosis.J Proteome Res, vol. 14, no. 2, Feb. 2015, pp. 1238–49. Pubmed, doi:10.1021/pr501149m.
Foster MW, Morrison LD, Todd JL, Snyder LD, Thompson JW, Soderblom EJ, Plonk K, Weinhold KJ, Townsend R, Minnich A, Moseley MA. Quantitative proteomics of bronchoalveolar lavage fluid in idiopathic pulmonary fibrosis. J Proteome Res. 2015 Feb 6;14(2):1238–1249.
Journal cover image

Published In

J Proteome Res

DOI

EISSN

1535-3907

Publication Date

February 6, 2015

Volume

14

Issue

2

Start / End Page

1238 / 1249

Location

United States

Related Subject Headings

  • Tandem Mass Spectrometry
  • Reproducibility of Results
  • Proteomics
  • Idiopathic Pulmonary Fibrosis
  • Humans
  • Electrophoresis, Polyacrylamide Gel
  • Bronchoalveolar Lavage Fluid
  • Biochemistry & Molecular Biology
  • 34 Chemical sciences
  • 31 Biological sciences